Estudos de não-inferioridade são modelos experimentais desenvolvidos com o objetivo de determinar se um novo tratamento ou procedimento não é menos eficaz que outro já estabelecido e considerado como controle. São de grande importância no estudo de tratamentos em que o uso de placebo é inviável. Requerem metodologia diferente dos estudos clássicos, chamados de estudos de superioridade, especialmente no planejamento e análise estatística. O presente artigo é uma revisão dos principais elementos diferenciais entre estudos de não-inferioridade e estudos tradicionais. Existe ainda em nosso meio um considerável grau de desconhecimento sobre o uso correto dessa metodologia, o que certamente compromete a validade de alguns estudos clínicos.

Biological products; similar/drug effects; heparin, low molecular weight; guidelines; drug evaluation. and hip arthroplasty), as a clinical model of higher sensitivity to detect potential effectiveness differences. The incidence of events in these indications is higher and reasonably well known, which allows a better study planning. It is estimated that in major orthopedic surgeries, the risk of venous thromboembolism without prevention is around 40 to 70% 3 and that the use of LMWH decreases this risk by about 60% 4. Thus, it can be estimated that in prevention studies in these cases, the incidence of events must be around 15 to 25% and that in these conditions, studies of non-inferiority with a margin of 5 to 10% must require clinical studies with 600 to 1,200 patients. If the expected incidence of events is decreased to, for instance, 5%, as it occurs in low-risk interventions, the sample size necessary for the study, while maintaining the same statistical properties, will be around 3,700 patients. Another guideline on the same subject was issued by the South Asian Society on Atherosclerosis & Thrombosis (SASAT) 5. This organization basically endorses the EMEA position, being, however, more stringent regarding the clinical studies, stipulating the need to include two randomized and doubleblind studies-one on venous thromboembolism and another on arterial thromboembolism.

Biological products or biopharmaceuticals are medicinal products derived from living systems and manufactured by modern biotechnological methods that differ widely from the traditional synthetic drugs. Monoclonal antibodies are the most rapidly growing type of biologic. They are much larger and more complex molecules with inherent diversity; therefore, different manufacturers cannot produce identical biological products, even with the same type of host expression system and equivalent technologies. Thus, legal follow-on biologics manufactured and marketed after patent expiration are usually referred to as biosimilars. Biosimilarity is based on a comparability exercise whereby unavoidable clinical differences are evaluated and must meet equivalence or non-inferiority criteria. Biosimilars need to comply with different regulatory requirements for market authorization in different sites. There are several other related issues that need to be defined by the national authorities, such as interchangeability, labeling and prescribing information. The Brazilian health surveillance agency follows the key principles established by the World Health Organization for the assessment of biosimilarity, although does not adopt the name ‘biosimilar’. However, the agency also made a compromise on a standalone application pathway that does not require the usual comparability exercise with the reference product, originating nonbiosimilar copies. Interchangeability and the use of nonproprietary names are not regulated, giving rise to pressures on physicians and conflicts of interest in the decision making on biosimilar use. The scope of this article is to present the Brazilian regulation on biosimilars, its strengths and weaknesses, and to discuss it in the face of regulations in the USA and Europe.

Letter to editor Non-inferiority versus equivalence clinical trials in assessing biological products Estudos de clínicos de não inferioridade versus equivalência na avaliação de produtos biológicos